Anti-Cancer Agents in Medicinal Chemistry

The fact that cancer is the greatest challenge for medicine of the twenty-first century is undebatable. Moreover, it represents a hot topic not only in the medico-pharmaceutical research but scientist belonging to other different connected fields like chemistry, physics, informatics work together in order to find a good strategy to make advances in the endeavor to defeat this hard-to-beat enemy. The latest statistic of WHO details the fact that cancer is the second leading cause of death globally. Up to date the most common approaches include surgery, chemotherapy, radiation therapy, and immunotherapy. It is well known the fact that Plant Kingdom has played a vital role in the design of active chemotherapeutic agents. In the history of natural compounds used in clinical trials for the cytotoxic activity they are some well known ‘protagonists’ including: vinca alkaloids, paclitaxel, homoharringtonine and their derivatives. Also an increased number of semisynthetic derivatives of plant secondary metabolites are in clinical trials for different types of cancer. FDA data show that approximately 40% of the approved molecules in the pharmaceutical market are natural compounds or their chemical derivatives from which, 74% are employed in well-established protocols of anticancer therapy. Moreover, recent studies show that a significant number of natural compounds are ‘cancer-selective’ presenting antiproliferative, pro-apoptotic, cytotoxic potential against cancerous cells without any effect against normal, healthy cells. Because the biodiversity of our planet has not been fully exploited, Plant Kingdom represents a big pool for the discovery of anti-cancer agents. Having this alive proofs about the role of natural compounds in the management of this highly aggressive pathology, this special thematic issue of Anti-Cancer Agents in Medicinal Chemistry was aimed to cover the recent trends and advancements in the field of natural bioactive compounds, vegetal extracts and modern pharmaceutical formulations with anti-cancer potential. The group of Wiemann et al., presents a review of the most important findings on the cytotoxic behavior of dehydroabietylamine derivatives, natural compounds belonging to the chemical class of diterpenes; the manuscript also points several drawbacks of some of these compounds such as low bioavailability and/or poor solubility. The work focuses on the chemical aspects and summarizes the related biological effects of the aforementioned structures [1]. With their work, Sharma et al. update about the management of cervical cancer by the help of natural compounds. The present report reveals pharmacokinetic/pharmacodynamics aspects of various pipeline drugs that have a prominent hope for the treatment of cervical cancer. Moreover, the study exposes the possible mechanism, adverse drug reaction, combined therapy and pleiotropic action of these under investigational drugs, which can further improve the therapeutic efficacy and restrict the imaginable harmful effects [2]. In their review Fayyaz et al., present the latest data regarding the potential of blueberry as natural inhibitor of metastasis and powerful apoptosis inducer. The main mechanism of action and chemical pathways are underlined [3]. Binienda et al., highlight the latest findings regarding the anticancer properties of silibinin, focusing on the molecular mechanism and therapeutic effect in breast cancer. Also, a discussion about silibinin and commonly-used anti-cancer drugs - co-treatment is included [4]. The comprehensive review of Betul Yerer et al., emphasizes current data about the anticancer effects of coumarins and their hybrid molecules including novel pharmaceutical formulations focusing on the structure-activity relationship of these compounds in cancer. Based on ISI Web of Science data, the manuscript shows the importance and the increased number of studies of this class on secondary plant metabolites in different anti-cancer approaches in the last ten years [5]. Mandadi N. Reddy et al., present an in depth phytochemical and biological characterization of the fern Tectaria coadunate. The work describes the in vitro antiproliferative potential of the plant crude extract using three different leukemic cell lines (KG1, MOLT-3 and K-562) [6]. The in-depth review of Antal et al., provides an outline of the various ways in which flavonolignans advance the combat against cancer. Different molecular targets are underlined. A paragraph that depicts the synergistic efficacy with some consecrated anti-cancer agents is also included. While the main focus falls on flavonolignans from milk thistle, attention is drawn to the yet underexplored potential of less known flavonolignan subgroups derived from isoflavonoids and aurones [7]. The work of Senapathy et al., explores an interesting approach, namely the role of phytochemicals that can acts as photosensitizers alone or in combination with photodynamic therapy and their mechanism of action on different types of cancer [8].

Advancement in Anti-Cancer Drug Discovery: Perspective of Interdisciplinary Research in Synthetic, Natural, In Silico Computational Chemistry, Nano-Anti-Cancer Drugs and Bio-Molecules Based Therapeutic

Cancers constitute the most serious of the unresolved health issues. Due to their complexity, cancers are very difficult to eradicate. This group of diseases has a great global spread in terms of morbidity and mortality, causing millions of deaths and hundreds of thousands of new cases each year. In fact, according to the GLOBOCAN project, approximately 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 [1]. Meanwhile, estimates in 2014 indicated that the same amount of people were expected to develop cancer [2]. Through the process known as drug discovery, scientific advances have provided chemotherapeutic options to fight against different kinds of cancers. However, drug discovery is an expensive and time-consuming process. At the same time, the emergence of resistance to current anti-cancer drugs, and the side effects associated with chemotherapeutic treatments are two factors that raise concerns. Consequently, the scientific community currently working in cancer research faces great challenges toward the discovery of new, versatile, and efficient anticancer drugs. Nowadays, it seems that new methodologies should be introduced in order to design more effective and safer anti-cancer drugs. Simultaneously, current approaches must be revisited in the sense of exploring new concepts and experimental evidence for ‘old cancer-related targets’. Therefore, the present special issue is devoted to giving an overview of different visions in cancer research. It is known that at the molecular level, p53 can be considered the guardian of the genome [3], and thus the first article of this special issue analyzes the effect of different chemicals on the regulation of different cell death pathways via nucleocytoplasmic shuttling of p53. A second article deals with the application of the Monte Carlo technique [4], which is used to perform virtual screening of anti-cancer compounds. Three pieces of research focus on the role natural products (NPs) as constant sources of anti-cancer drugs [5-8]. In this sense, one of these works discusses relevant aspects associated with the anticancer activity such as species origin, druglikeness, target, and pathways. Another report reviews the application of different virtual screening methods used in the search for anti-cancer NPs, where secondary metabolites are briefly discussed. Finally, an article is devoted to providing an updated perspective regarding the importance of phytochemicals for anticancer drug development. Articles in this special issue mention promising alternative approaches that can be used to integrate diverse kinds of chemical and biological data from a multi-scale perspective with the aim of designing potent and safer drugs [9-14]. Such approaches can be successfully applied to anticancer drug discovery, and they open new horizons because all the essential stages of drug discovery can be considered simultaneously: from protein inhibitors to compounds with the potential to become clinical candidates [15-20]. The Guest Editor would like to acknowledge the time and effort of the authors, reviewers, members of the Editorial Board, as well as the members of the Production and Management Departments, who have contributed to this special issue.

Cancer is a terrible disease of the century which make a lot of deaths, worldwide. This is why, many researchers are trying to find solutions or the increase the efficiency of the existent ones. The development of new antitumoral agents is essential but require a lot of work (research including synthesis, extractions, purifications, etc.), time and resources so, a more efficient administration of the existent agents could be of interest. Drug delivery and especial targeted drug delivery are increasingly used in improving the antitumoral efficiency and to reduce the side effects at non-desired sites. A special attention will be paid for the use of natural compounds with antitumoral activity. Depending on the nature of the active agent, the nature of the cancerous tissue/organ and the characteristics of the normal and pathogen body fluids, etc., the design of the drug delivery systems will be made such as to assure the best efficiency. It is desired that the active agents to be released only in a targeted way (only in the tumoral region of the tissue/organ). Morphological and compositional design will assure the above mentioned characteristics. An interesting aspect of these delivery systems, with increasing interest for the researchers and clinicians, is related to the involvement of the “external and internal triggered-stimuli”. pH, thermal and magnetical stimuli are especially used for adjusting the delivery characteristics and can be also applied for cancer therapy. Antitumoral systems with multiple mechanisms of action are welcome because can enhance the overall antitumoral activity and can assure a long term antitumoral activity with lower side effects.

Cancer is classified as a complex and heterogeneous collection of disease with over 100 different types of cancer. Numerous medicinal plants have been reported to have anticancer effect and effort for finding new anticancer agents with better efficacy and lesser side effects is still going on. Due to increasing cost of drug development, there is an urgent need for innovative approaches for target identification and efficacy prediction to uncover the therapeutic effect of drugs. A network-based approach is expected to offer important insights into the relationship between plants based active products and anticancer targets. In recent times, a renewed interest in understanding metabocentric adaptation occurring in the cancer cells vis-à-vis inflammation, angiogenesis and metastasis has been observed. Given the functional interdependencies between anti-cancer molecular targets and phytochemicals, emerging tools of network medicine offer a platform to explore systematically complexity of cancer biology, drug targets and therapeutic use of phytochemicals. In the special issue we invite the researchers to contribute original and review articles regarding network-based drug discovery, anti-cancer molecular targets and therapeutic use of phytochemicals

To give an overview of current indications and criticism on Active Surveillance for prostate cancer and small renal masses

Aims & Scope: In spite of the major progress made in the medical world to treat cancer, the existing therapies lack in terms of selectivity, and some cancers are infact resistant to the existing therapies. Plasma treatment is gaining increasing interest, because it is stated to selectively treat cancer cells, and no resistance against plasma treatment has been observed yet. Most studies are still in vitro and in vivo and few existing clinical trials. Cold atmospheric plasma activated solution, on the other hand, can more generally be used where cold atmospheric plasma (CAP) device is not available, and it is also less dependent on the treatment conditions. Additionally, Cold atmospheric plasma activated solution can be injected into the tissues and thus prevent tumor growth more effectively than CAP devices. This special issue will help increase the understanding about the underlying mechanisms of Cold atmospheric plasma activated solution, but also enhance the possibilities to apply plasma medicine for cancer therapy.

Aims & Scope: The mini-hot topic issue will include reviews about both natural and chemical compounds used for the chemoprevention of different types of cancer. Mechanism of action will be discussed, including the antiproliferative, pro-apoptotic and inflammation-associated cancerogenesis. A special direction will be held towards mitochondria-targeted anticancer agents.A review of a new modern method of topical administration for antitumor skin active compounds, namely electoporation will be also depicted. The aims & scope of this special issue is to describe the latest news and trends in various types of cancer chemopreventive. An important place in this overview is allocated for skin cancer

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